Fig. 8: Abnormalities of neuronal metabolism in the brains of Tak1 CKO mice.
From: Reduction of neuronal activity mediated by blood-vessel regression in the adult brain
a The morphology of mitochondria in synapses from control and Tak1 CKO mice (Cdh5-CreER::Tak1fl/fl). SV, synaptic vesicles. MT, mitochondria. b Summarized results (mean ± SEM) of mitochondrial features in control and Tak1 CKO mice. Y-axis, the number of cristae was normalized to the surface of mitochondria. ***, p < 0.005, unpaired Student’s t-test. c Principal component analysis (PCA) of the metabolomes of control (Ctrl) and Tak1 CKO samples. d A heatmap representation of 20 metabolites (VIP score > 1, i.e., Variable Importance in Projection) in the cerebral cortex of five control (Ctrl) and five Tak1 CKO mouse brains. Color bar (bottom left) indicates the scale of standardized metabolite levels. Warm color indicates higher concentration. NAD+ Nicotinamide adenine dinucleotide; dAMP deoxyadenosine monophosphate; GSSG oxidized glutathione; GPC Glycerophosphocholine; R5P Ribose 5-phosphate (Ctrl group, n = 5 mice; CKO group, n = 5 mice). e, f Schematic illustrating all metabolites in the tricarboxylic acid cycle (TCA). Blue arrows indicate a decrease of these metabolites (highlighted in red) in Tak1 CKO mouse brains. Metabolites without arrows (black), no significant difference. Relative abundance (normalized by TIC of the control group) of the metabolites shown in e from control (light blue) and Tak1 CKO (magenta) samples. *, p < 0.05, **, p < 0.01, ***, p < 0.005; two-tailed unpaired Student’s t-test. FAD, flavin adenine dinucleotide. g Volcano plot representing significantly up- and down-regulated genes. Padj, adjusted p value. Ctrl (n = 4 mice) and Tak1 CKO (n = 4 mice). Up-regulated and down-regulated genes are highlighted in pink and light blue, respectively. Core genes in the “Glutamatergic Synapse” gene set are in bold; blue represents genes with significant differential expression, while brown represents genes with no significant difference, two-tailed t-tests. h Color scale heatmap showing the normalized expression of core genes of the Glutamatergic Synapse gene set, which is significantly down-regulated in the Tak1 CKO group vs Ctrl. i GSEA plots of Glutamatergic Synapse gene set, with black bars indicating gene sets represented among all genes pre-ranked by ranking metrics (Ctrl versus Tak1 CKO), with indicated normalized enrichment score (NES) and false discovery rate (FDR) q-value.
